Detection and Clinical Significance of Intratumoral EGFR Mutational Heterogeneity in Chinese Patients with Advanced Non-Small Cell Lung Cancer
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{"title"=>"Detection and Clinical Significance of Intratumoral EGFR Mutational Heterogeneity in Chinese Patients with Advanced Non-Small Cell Lung Cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Hua", "last_name"=>"Bai", "scopus_author_id"=>"35277169800"}, {"first_name"=>"Zhijie", "last_name"=>"Wang", "scopus_author_id"=>"35735553200"}, {"first_name"=>"Yuyan", "last_name"=>"Wang", "scopus_author_id"=>"54786045200"}, {"first_name"=>"Minglei", "last_name"=>"Zhuo", "scopus_author_id"=>"26634626600"}, {"first_name"=>"Qinghua", "last_name"=>"Zhou", "scopus_author_id"=>"7402700107"}, {"first_name"=>"Jianchun", "last_name"=>"Duan", "scopus_author_id"=>"15756795300"}, {"first_name"=>"Lu", "last_name"=>"Yang", "scopus_author_id"=>"57190687938"}, {"first_name"=>"Meina", "last_name"=>"Wu", "scopus_author_id"=>"55597273500"}, {"first_name"=>"Tongtong", "last_name"=>"An", "scopus_author_id"=>"7004833021"}, {"first_name"=>"Jun", "last_name"=>"Zhao", "scopus_author_id"=>"57127351700"}, {"first_name"=>"Jie", "last_name"=>"Wang", "scopus_author_id"=>"7701310371"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368342495", "sgr"=>"84873887494", "pmid"=>"23418425", "scopus"=>"2-s2.0-84873887494", "doi"=>"10.1371/journal.pone.0054170", "issn"=>"19326203"}, "id"=>"42d645b1-8d60-357b-ab50-389b9288bafa", "abstract"=>"PURPOSE: This study evaluated occurrence and potential clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with non-small cell lung cancer (NSCLC).\\n\\nMATERIALS AND METHODS: Eighty-five stage IIIa-IV NSCLC patients who had undergone palliative surgical resection were included in this study. Of these, 45 patients carried EGFR mutations (group-M) and 40 patients were wild-type (group-W). Each tumor sample was microdissected to yield 28-34 tumor foci and Intratumoral EGFR mutation were determined using Denaturing High Performance Liquid Chromatography (DHPLC) and Amplification Refractory Mutation System (ARMS). EGFR copy numbers were measured using fluorescence in situ hybridization (FISH).\\n\\nRESULTS: Microdissection yielded 1,431 tumor foci from EGFR mutant patients (group-M) and 1,238 foci from wild-type patients (group-W). The EGFR mutant frequencies in group-M were 80.6% (1,154/1,431) and 87.1% (1,247/1,431) using DHPLC and ARMS, respectively. A combination of EGFR-mutated and wild-type cells was detected in 32.9% (28/85) of samples by DHPLC and 28.2% (24/85) by ARMS, supporting the occurrence of intratumoral heterogeneity. Thirty-one patients (36.5%) were identified as EGFR FISH-positive. Patients harboring intratumoral mutational heterogeneity possessed lower EGFR copy numbers than those tumors contained mutant cells alone (16.7% vs. 71.0%, P<0.05). Among 26 patients who had received EGFR-TKIs, the mean EGFR mutation content was higher in patients showing partial response (86.1%) or stable disease (48.7%) compared with patients experiencing progressive disease (6.0%) (P = 0.001). There also showed relationship between progression-free survival (PFS) and different content of EGFR mutation groups (pure wild type EGFR, EGFR mutation with heterogeneity and pure mutated EGFR) (P = 0.001).\\n\\nCONCLUSION: Approximately 30% of patients presented intratumoral EGFR mutational heterogeneity, accompanying with relatively low EGFR copy number. EGFR mutant content was correlated with the response and prognosis of EGFR-TKIs.", "link"=>"http://www.mendeley.com/research/detection-clinical-significance-intratumoral-egfr-mutational-heterogeneity-chinese-patients-advanced", "reader_count"=>12, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>3, "Student > Master"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>3, "Student > Master"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "Japan"=>1}, "group_count"=>1}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/489401"], "description"=>"<p>The different color of pie represent different EGFR mutation heterogeneity. The left three parts (lightblue, purple and green) of each pie chart represent percentage of cases with EGFR heterogeneity.</p>", "links"=>[], "tags"=>["egfr", "mutation", "dhplc"], "article_id"=>159906, "categories"=>["Cell Biology", "Biotechnology", "Cancer", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Hua Bai", "Zhijie Wang", "Yuyan Wang", "Minglei Zhuo", "Qinghua Zhou", "Jianchun Duan", "Lu Yang", "Meina Wu", "Tongtong An", "Jun Zhao", "Jie Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054170.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heterogeneity_of_EGFR_mutation_by_DHPLC_and_ARMS_/159906", "title"=>"Heterogeneity of EGFR mutation by DHPLC and ARMS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:25:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/489586"], "description"=>"<p>The various <i>EGFR</i> mutation contents are depicted in the legend.</p>", "links"=>[], "tags"=>["heterogeneity"], "article_id"=>160100, "categories"=>["Cell Biology", "Biotechnology", "Cancer", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Hua Bai", "Zhijie Wang", "Yuyan Wang", "Minglei Zhuo", "Qinghua Zhou", "Jianchun Duan", "Lu Yang", "Meina Wu", "Tongtong An", "Jun Zhao", "Jie Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054170.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extent_of_EGFR_heterogeneity_as_measured_by_FISH_/160100", "title"=>"Extent of <i>EGFR</i> heterogeneity as measured by FISH.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:26:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/489502"], "description"=>"<p>The left graph showed routine EGFR mutation status detection by DHPLC and corresponding bulk tissue. The right graph represent EGFR mutation heterogeneity by microdissection. The above two panels represent mutant EGFR in bulk tissues showed pure mutation and mutation with heterogeneity by microdissection, respectively. The below two panels represent wild EGFR in bulk tissues with pure wild-type EGFR or mixed with low frequency of mutation cells by microdissection.</p>", "links"=>[], "tags"=>["intratumoral"], "article_id"=>160018, "categories"=>["Cell Biology", "Biotechnology", "Cancer", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Hua Bai", "Zhijie Wang", "Yuyan Wang", "Minglei Zhuo", "Qinghua Zhou", "Jianchun Duan", "Lu Yang", "Meina Wu", "Tongtong An", "Jun Zhao", "Jie Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054170.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_representative_example_of_intratumoral_EGFR_genetic_heterogeneity_/160018", "title"=>"A representative example of intratumoral <i>EGFR</i> genetic heterogeneity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:26:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/489713"], "description"=>"<p>Patient characteristics.</p>", "links"=>[], "tags"=>["genetics and genomics", "public health and epidemiology", "Computational biology", "oncology", "Evolutionary biology", "pathology"], "article_id"=>160222, "categories"=>["Cell Biology", "Biotechnology", "Cancer", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Hua Bai", "Zhijie Wang", "Yuyan Wang", "Minglei Zhuo", "Qinghua Zhou", "Jianchun Duan", "Lu Yang", "Meina Wu", "Tongtong An", "Jun Zhao", "Jie Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054170.t001", "stats"=>{"downloads"=>8, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_characteristics_/160222", "title"=>"Patient characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 15:27:35"}

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Relative Metric

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